Pulse and active pulse spectraphotometry

ABSTRACT

A pulse and active pulse spectraphotometry system comprises a light source adapted to illuminate a tissue site with optical radiation having a plurality of wavelengths selected from at least one of a primary band and a secondary band. The tissue site has a modulated blood volume resulting from the pulsatile nature of arterial blood or from an induced pulse. A detector is configured to receive the optical radiation attenuated by the tissue site and to generate a detector output responsive to absorption of the optical radiation within the tissue site. A normalizer operating on the detector output generates a plurality of normalized plethysmographs corresponding to the plurality of wavelengths. Further, a processor is configured to calculate a ratio of fractional volumes of analytes in the blood volume based upon the normalized plethysmographs.

REFERENCE TO RELATED APPLICATION

The present application claims priority benefit under 35 U.S.C. §119(e)from U.S. Provisional Application No. 60/358,809, filed Feb. 22, 2002,entitled “Pulse and Active Pulse Spectraphotometry,” which isincorporated herein by reference.

BACKGROUND OF THE INVENTION

Various spectral photometric techniques have been developed for thenoninvasive monitoring of blood constituent concentrations. In suchsystems, light of multiple wavelengths is used to illuminate a thintissue portion of a person, such as a fingertip or earlobe. A spectrumanalysis of light transmitted through or reflected from the tissueportion is used to measure the light absorption characteristics of bloodflowing through the tissue portion. Utilizing calibration data, theconcentration of various blood constituents is then derived from knownlight absorption characteristics of these blood constituents. In onespectral photometric methodology, the absolute optical spectrum of lightreceived from the tissue portion is measured. In a differential spectralphotometric methodology, blood constituent concentrations are derivedfrom photoplethysmograph data that is responsive to blood volumechanges. Pulse oximetry systems, which use the latter methodology tomonitor hemoglobin constituents, have been particularly successful inbecoming the standard of care for patient oxygen saturation monitoring.

SUMMARY OF THE INVENTION

Spectraphotometry for the noninvasive monitoring of blood constituents,such as blood glucose and total hemoglobin, to name a few, is highlydesirable. For example, current methods for accurately measuring bloodglucose involve drawing blood from the subject, which can be onerous fordiabetics who must take frequent samples to closely monitor bloodglucose levels. Spectraphotometry is described under no scatteringconditions by the Beer-Lambert law, which states that the concentrationc_(i) of an absorbant in solution can be determined by the intensity oflight transmitted through the solution, knowing the pathlength d_(λ),the intensity of the incident light I_(0,λ), and the extinctioncoefficient ε_(i,λ) at a particular wavelength λ. The generalizedBeer-Lambert law is expressed as $\begin{matrix}{I_{\lambda} = {I_{0,\lambda}{\mathbb{e}}^{{- d_{\lambda}} \cdot \mu_{a,\lambda}}}} & (1) \\{\mu_{a,\lambda} = {\sum\limits_{i = 1}^{n}\quad{ɛ_{i,\lambda} \cdot c_{i}}}} & (2)\end{matrix}$where μ_(a,λ) is the bulk absorption coefficient and represents theprobability of absorption per unit length. Dividing both sides of EQ. 1by I_(0,λ) and taking the logarithm yields $\begin{matrix}{{\ln\quad\left( \frac{I_{\lambda}}{I_{0,\lambda}} \right)} = {{- d_{\lambda}} \cdot \mu_{a,\lambda}}} & (3)\end{matrix}$For n wavelengths, EQS. 2 and 3 can be expressed as $\begin{matrix}{\begin{bmatrix}{\ln\quad\left( \frac{I_{\lambda_{1}}}{I_{0,\lambda_{1}}} \right)} \\\vdots \\{\ln\quad\left( \frac{I_{\lambda_{n}}}{I_{0,\lambda_{n}}} \right)}\end{bmatrix} = {- {{d\begin{bmatrix}ɛ_{1,\lambda_{1}} & \cdots & ɛ_{n,\lambda_{1}} \\\vdots & ⋰ & \vdots \\ɛ_{1,\lambda_{n}} & \cdots & ɛ_{n,\lambda_{n}}\end{bmatrix}}\begin{bmatrix}c_{1} \\\vdots \\c_{n}\end{bmatrix}}}} & (4)\end{matrix}$assuming the pathlength is approximately constant at the wavelengths ofinterest, i.e. d_(λ) ₁ =d_(λ) ₁ =. . . d_(λ) _(n) =d. EQ. 4 can berewritten asI(λ)=−dA(λ)C  (5)Solving for the constituent concentrations yields $\begin{matrix}{C = {{- \frac{1}{d}}{A(\lambda)}^{- 1}{I(\lambda)}}} & (6)\end{matrix}$

As is well known in the art, a system of linear equations can be solvedif there are as many linearly independent equations as unknowns. Appliedto EQ. 6, the concentration of a particular blood constituent can becalculated if the number of discrete wavelengths used is equal to thenumber of significant absorbers that are present and if the absorptioncharacteristics of the significant absorbers are distinguishable atthese wavelengths.

FIG. 1 is a hemoglobin extinction graph 100 illustrating the applicationof the Beer-Lambert law to pulse oximetry. The extinction graph 100 hasan extinction coefficient axis 101 in units of cm⁻¹/mole and awavelength axis 102 in units of nm. An Hb curve 110 and an HbO₂ curve160 show the light absorption (extinction) properties of reducedhemoglobin and oxyhemoglobin, respectively. In particular, Hb and HbO₂have significantly different absorption characteristics in the red tonear IR wavelengths. Indeed, Hb absorption 110 is greater than HbO₂absorption 160 in the red spectrum and, conversely, HbO₂ absorption 160is greater than Hb absorption 110 in the near IR spectrum. At red andnear IR wavelengths below 970 nm, where water has a significant peak,hemoglobin species are the only significant absorbers. Further, Hb andHbO₂ normally are the only hemoglobin species having significantconcentrations in blood. Thus, only two wavelengths are needed toresolve the concentrations of Hb and HbO₂. Further, if one redwavelength and one IR wavelength are used, the absorptioncharacteristics of Hb and HbO₂ are different enough at these wavelengthsto resolve the concentrations of Hb and HbO₂. Typically, a pulseoximetry sensor utilizes a red emitter, such as a light emitting diode(LED) operating at 660 nm, and an IR emitter, such as a LED operating at905 nm. As a practical matter, pulse oximetry does not explicitlycompute a solution to EQ. 6, but computes a ratio of concentrations sothat the pathlength, d, may be cancelled, as described with respect toEQ. 7, below.

FIG. 2 is an absorption chart 200 illustrating the absorption propertiesof various tissue site components. The absorption chart 200 has a totalabsorption axis 201 and a time axis 202. Total absorption 201 isattributed to time-invariant absorption layers 210 and a time-variantabsorption layer 260. The time-invariant absorption layers 210 include atissue absorption layer 220, which includes skin, muscle, bone, fat andpigment; a venous blood absorption layer 230; and a baseline arterialblood absorption layer 240. The time-variant absorption layer 260 is dueto the pulse-added volume of arterial blood, i.e. the differentialvolume of arterial blood due to the inflow during systole and theoutflow during diastole. The time-variant absorption layer 240 has aplethysmograph absorption profile 270.

Pulse oximetry relies on the pulsatile nature of arterial blood todifferentiate blood constituent absorption from absorption of otherconstituents in the surrounding tissues. That is, the sensor signalgenerated by the pulse-added arterial blood layer 260 is isolated fromthe signal generated by other layers 210, including tissue, venous bloodand baseline arterial blood. To do this, pulse spectraphotometrycomputes a ratio of the AC portion of the detected signal, which is dueto the time-variant layer 260, with respect to the DC portion of thedetected signal, which is due to the time-invariant layers 210, for eachof multiple wavelengths. Computations of AC/DC ratios provide relativeabsorption measures that compensate for variations in both incidentlight intensity and background absorption and, hence, are responsiveonly to the hemoglobin in the arterial blood. As an example, pulseoximetry typically computes a red (RD) AC/DC ratio and an IR AC/DCratio. Then, a ratio of ratios is computed, i.e.RD/IR=(AC_(RD)/DC_(RD))/(AC_(IR)/DC_(IR))  (7)

The desired oxygen saturation measurement is then computed empiricallyfrom this RD/IR ratio.

In general, pulse spectraphotometry uses multiple wavelength absorptionmeasures, where the number and value of the wavelengths are based on thenumber of significant absorbers (analytes) and the absorptioncharacteristics of these analytes. Further, pulse spectraphotometryexploits the plethysmograph absorption profile of arterial blood tocancel the time-invariant absorption contributions from other tissuecomponents and normalization to account for variations in incident lightat the different wavelengths. In particular, pulse oximetry systems aregenerally recognized as providing an accurate measurement of bloodoxygen through a comparative measurement of oxyhemoglobin and reducedhemoglobin constituents. The application of pulse spectraphotometry tothe accurate measurement of other blood constituents, such as glucoseconcentration or total hemoglobin, however, poses a number ofdifficulties, as described below.

FIG. 3 illustrates is an absorption graph 300 for water in the nearinfrared (IR) spectrum. The absorption graph 300 has an absorptioncoefficient axis 301 in units of cm⁻¹ and a wavelength axis 302 in unitsof nm. Biological tissues contain a significant percentage of water.Thus, the combination of the light absorption and scatteringcharacteristics of water largely determine the useful range ofwavelengths for pulse spectraphotometry. A water absorption curve 310shows that water absorption increases rapidly with increasing wavelength302 in the near IR, i.e. in the 750 nm to 3000 nm wavelength range.Fortunately for pulse oximetry, water is not a significant absorbercompared with hemoglobin in the red and small wavelength portion of thenear infrared, i.e. in the 660 to 940 nm wavelength range. Water,however, is a significant absorber in the larger wavelength portion ofthe near infrared and beyond. In particular, the penetration depth inwater of wavelengths around about 1400 nm is 1 mm or less, and thepenetration depth decreases rapidly with increasing wavelength beyond1400 nm.

Some of the blood constituents of interest are not significant absorbersin the range of wavelengths where photons can penetrate biologicaltissue. For example, glucose is not a significant absorber in thevisible spectrum. Glucose does have strong absorption bands in the farIR, having an absorption peak at 9700 nm, but photon penetration depthat that wavelength is on the order of 10 μm, i.e. around three orders ofmagnitude less than in the visible and near IR bands used in pulseoximetry.

When very little analyte is present, such as for blood glucose, theresulting low signal-to-noise ratio (SNR) represents an inherent systemlimitation for pulse spectraphotometry in the near IR. Further, thereare multiple blood constituents, such as hemoglobin, cholesterol andvarious proteins, such as albumin and gammaglobulins that aresignificant absorbers in the near IR. Thus, unlike pulse oximetry, morethan two wavelengths are required to resolve a particular analyte atthese wavelengths.

One aspect of a pulse spectraphotometry system is a light source adaptedto illuminate a tissue site with optical radiation having a plurality ofwavelengths selected from at least one of a primary band and a secondaryband, where the tissue site has a modulated blood volume. A detector isconfigured to receive the optical radiation attenuated by the tissuesite and to generate a detector output responsive to absorption of theoptical radiation within the tissue site. A normalizer operating on thedetector output generates a plurality of normalized plethysmographscorresponding to the plurality of wavelengths. Further, a processor isconfigured to calculate a ratio of fractional volumes of analytes in theblood volume based upon the normalized plethysmographs. In a preferredembodiment, the primary band is in a range of about 1620 nm to about1730 nm and the secondary band is in a range of about 1000 nm to about1380 nm. In a more preferred embodiment, the primary band is in a rangeof about 1620 nm to about 1670 nm. In a most preferred embodiment, atleast one of the wavelengths is selected in a range of about 1650 nm±5nm, in a range of about 1032 nm±5 nm, in a range of about 1097 nm±5 nmor in a range of about 1375 nm±5 nm.

Another aspect of a pulse spectraphotometry system is a pulsespectraphotometry method comprising the steps of illuminating a tissuesite having a pulsatile blood flow with a narrowband optical radiation,time division multiplexing the optical radiation over a plurality ofwavelengths and selecting at least a portion of the wavelengths within arange of about 1620 nm to about 1730 nm. Further steps include detectingan attenuated optical radiation from the tissue site as the result ofthe illuminating step and calculating a ratio of analytes in the bloodflow based upon the attenuated optical radiation. In a preferredembodiment, the selecting step comprises the substep of selecting atleast one wavelength in a range of about 1620 nm to about 1670 nm. In amore preferred embodiment, the selecting step comprises a substep ofselecting at least one wavelength in a range of about 1650 nm±5 nm. Inanother preferred embodiment, the pulse spectraphotometry methodcomprises the further step of selecting a second portion of thewavelengths within a range of about 1000 nm to about 1380 nm. In anothermore preferred embodiment, the selecting a second portion step comprisesa substep of selecting at least one wavelength in a range of about 1032nm±5 nm, in a range of about 1097 nm±5 nm or in a range of about 1375nm±5 nm.

Yet another aspect of a pulse spectraphotometry system is an opticalradiation means for illuminating a tissue site and a filter means fordetermining a nominal wavelength of the optical radiation, where thenominal wavelength is selected from a range of about 1620 nm to about1730 nm. The pulse spectraphotometry system also has a detector meansfor receiving the optical radiation after transmission through orreflection from the tissue site and for generating a correspondingplethysmograph signal and a processor means for calculating a ratio ofanalyte portions of pulsatile blood flow within the tissue site basedupon the plethysmograph signal. In a preferred embodiment, the nominalwavelength is selected from a range of about 1620 nm to about 1670 nm.In a more preferred embodiment, the nominal wavelength is selected froma range of about 1650 nm±5 nm. In another preferred embodiment, thenominal wavelength is selected from a range of about 1000 nm to about1380 nm. In another more preferred embodiment, the nominal wavelength isselected from a range of about 1032 nm±5 nm, a range of about 1097 nm±5nm, or a range of about 1375 nm±5 nm. In yet another preferredembodiment, the nominal wavelength is selected from a range of about2000 nm to about 2500 nm.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph of oxyhemoglobin and reduced hemoglobin extinctioncoefficients versus wavelength;

FIG. 2 is a graph of total tissue and blood light absorption versustime;

FIG. 3 is a graph of water absorption versus wavelength across a portionof the near infrared spectrum;

FIG. 4 is a functional block diagram of a pulse spectraphotometrysystem;

FIG. 5 is a functional block diagram of a physiological sensor for pulsespectraphotometry; and

FIG. 6 is a graph of water and glucose absorption versus wavelengthincluding critical wavelength portions of the near infrared spectrum forpulse spectraphotometry.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

FIG. 4 illustrates a pulse spectraphotometry system having a signalprocessor 400 and a sensor 500. Herein, the term pulse spectraphotometryis intended to include spectraphotometry based upon the pulsatilecharacteristics of arterial blood, as described above, andspectraphotometry based upon an active pulse, as described below. Thesensor 500 is described in detail with respect to FIG. 5, below. Thesignal processor 400 has an analog-to-digital converter (ADC) 410, ademodulator 420, an active pulse control 430, a wavelength control 440,a timing control 450, a normalizer 460, a matrix calculator 480 and aratio calculator 490. The sensor 500 illuminates a tissue site 10 (FIG.5) with multiple wavelengths, one at a time, and generates a signaloutput 412 that is responsive to the intensity of optical radiationabsorbed by the tissue site 10 (FIG. 5). The signal output 412 is a timedivision multiplexed (TDM) signal with multiple time slots correspondingto the multiple wavelengths. The timing control 450 determines the timeslots. The ADC 410 digitizes the signal output 412, and the demodulator420 separates the individual time slots and corresponding responses. Thedemodulator output 422 is then normalized 470, such as by dividing theAC by the DC, as described above, to generate a normalizedphotoplethysmograph (NPP) 472.

Taking into account scattering in the tissue media and the resultingwavelength dependent optical pathlengths, the transmitted intensitythrough the media and, hence, the sensor signal output 412 can beapproximated asI _(λ) ≈A _(λ) e ^(−mpl) ^(λ) ^(·μ) ^(a,λ)   (8)which is similar in form to EQ. 1, described above, where A_(λ) is afunction of the incident light, the geometry of the tissue media and thetissue media composition; mpl_(λ) is the wavelength dependent meanpathlength; and μ_(a,) _(λ) is the bulk absorption coefficient expressedin EQ. 2, above. The NPP 472 can be derived from EQ. 8 as follows$\begin{matrix}{{d\quad I_{\lambda}} = {{- m}\quad{{pl}_{\lambda} \cdot A_{\lambda}}{{\mathbb{e}}^{{- m}\quad{{pl}_{\lambda} \cdot \quad\mu_{a,\lambda}}} \cdot d}\quad\mu_{a,\lambda}}} & (9) \\{{NPP} = {\frac{A\quad C_{\lambda}}{D\quad C_{\lambda}} = {\frac{d\quad I_{\lambda}}{I_{\lambda}} = {{- m}\quad{{pl}_{\lambda} \cdot d}\quad\mu_{a,\lambda}}}}} & (10)\end{matrix}$Assumedμ _(a,λ)≈μ_(ab) _(λ) ·ΔV/V  (11)where μ_(ab) _(λ) is the bulk absorption coefficient of the blood, V isthe tissue volume and ΔV is the change in tissue volume due to thepulsatile blood flow. EQ. 10 can then be written as $\begin{matrix}{\quad{{NPP} = {{- m}\quad{{pl}_{\lambda} \cdot \mu_{a,b_{\lambda}} \cdot v_{b}}}}} & (12) \\{{\mu_{a\quad b_{\lambda}} = {\sum\limits_{i}{v_{i} \cdot \mu_{i}}}};{{\sum\limits_{i}v_{i}} = 1}} & (13)\end{matrix}$which is similar in form to EQS. 2 and 3, described above, whereν_(b)=ΔV/V is the fractional blood volume. Also, ν_(i) is the fractionalvolume in the blood of the ith analyte and μ_(i) is the absorptioncoefficient of the ith analyte. For n wavelengths, EQS. 12 and 13 can beexpressed as $\begin{matrix}{\begin{bmatrix}{NPP}_{1} \\\vdots \\{NPP}_{n}\end{bmatrix} = {{- {{\begin{bmatrix}{mpl}_{\lambda_{1}} & \cdots & 0 \\\vdots & ⋰ & \vdots \\0 & \cdots & {mpl}_{\lambda_{n}}\end{bmatrix}\begin{bmatrix}\mu_{1,\lambda_{1}} & \cdots & \mu_{n,\lambda_{1}} \\\vdots & ⋰ & \vdots \\\mu_{1,\lambda_{n}} & \cdots & \mu_{n,\lambda_{n}}\end{bmatrix}}\begin{bmatrix}v_{1} \\\vdots \\v_{n}\end{bmatrix}}}v_{b}}} & (14)\end{matrix}$EQ. 14 can be rewritten asNPP=−MPL(λ)μ(λ)Vν _(b)  (15)Solving for the analyte fractional volumes yieldsV=−[MPL(λ)μ(λ)]⁻¹ NPP/ν _(b)  (16)which is similar in form to EQ. 6. The matrix calculator 480 performsthe matrix inversion indicated in EQ. 16. The ratio calculator 490 isthen used to cancel ν_(b) and determine a desired ratio of fractionalvolumes of analytes in the blood. The mean pathlengths can be determinedby calibration or separate measurements. A pathlength measurement methodis described in U.S. patent application Ser. No. 09/925,982 entitled“Optical Spectroscopy Pathlength Measurement System,” incorporated byreference herein. In particular, using the sensor 500 and thewavelengths described in detail with respect to FIG. 6, below, the ratiocalculator output 492 advantageously provides the ratio of thefractional volume of blood glucose to the fractional volume of water inthe blood, which is desired for diabetes diagnosis and monitoring.

Also shown in FIG. 4, an active pulse control 430 provides an activepulse control input to the sensor 500. Advantageously, an active pulsemechanism induces a periodic change in the flow of blood through atissue medium, which can provide a larger AC signal, as described withrespect to FIG. 2, above, and a greater SNR as a result. The degree ofblood flow modulation is determined by feedback from the NPP 472 so asto control the AC signal level. The active pulse mechanism is describedin further detail with respect to FIG. 5, below.

Further shown in FIG. 4, a wavelength control 440 provides a wavelengthcontrol input 442 to the sensor 500. The wavelength control 440 receivesinput from the timing control 450 and, accordingly, determines thewavelength sequence of optical radiation illuminating the tissue site 10(FIG. 5) in a manner analogous to the LED drive signals transmitted froma pulse oximetry monitor to a pulse oximetry sensor, which is well-knownin the art. The sensor wavelength control is described in further detailwith respect to FIG. 5, below.

FIG. 5 illustrates a pulse spectraphotometry sensor 500 having anambient light cover 502, a light source 510, a condensor lens 520, anarrow-band, multiple-wavelength filter 530, a mirror drive 540, acollecting lens 550, a fiberoptic cable 560, a detector 570, anamplifier 580 and an active pulse transducer 590. The light source 510and condensor lens 520 provide broadband optical radiation to thewavelength filter 530, which passes selected, narrowband portions of theoptical radiation to the collecting lens 550. The narrowband opticalradiation is coupled to the fiberoptic cable 560, which transmits thenarrowband optical radiation to illuminate a tissue site 10 that isshielded from ambient light by the cover 502. The detector 570 generatesa current proportional to the intensity of attenuated optical radiationreceived after transmission through or reflection from the illuminatedtissue site 10. The received intensity is responsive to the absorptioncoefficients of blood constituents, as described with respect to EQS.8-13, above. An amplifier 580 provides a gain in the detector currentand generates a signal output 412 to the processor 400 (FIG. 4),described above.

As shown in FIG. 5, the wavelength filter 530 has an input mirror 532,an output mirror 534, a parabolic mirror 536 and an optical filter array538. The input mirror 532 and output mirror 534 are rotatable accordingto drive signals 542 from the mirror drive 540. As such, the mirrordrive 540 controls the optical path of light around the parabolic mirror536 and through a particular optical filter in the optical filter array538. Each optical filter in the optical filter array 538 is manufacturedto a different narrow passband. Thus, the wavelength filter 530determines the nominal wavelength of optical radiation that illuminatesthe tissue site 10 at any particular time. The wavelength control input442 from the signal processor 400 (FIG. 4) synchronizes the timing ofthe input mirror 532 and output mirror 534 rotations and, accordingly,the tissue illumination wavelength and the characteristics of the TDMsignal output 412, described with respect to FIG. 4, above.

Also shown in FIG. 5 is the active pulse transducer 590, which modulatesthe blood flow at the tissue site 10 according to the active pulsecontrol input 432, described with respect to FIG. 4, above. In oneembodiment, the active pulse transducer is a pressure device applied toa patient's digit. The pressure device may be, for example, a cuffhaving a bladder that periodically fills and empties with a gas orliquid, such as air or water. Although shown separate from the sensor inFIG. 5, the transducer 590 may be an integral part of the sensor. Activepulse apparatuses and methods are described in U.S. Pat. No. 6,151,516entitled “Active Pulse Blood Constituent Monitoring,” incorporated byreference herein.

In one sensor embodiment, the light source 510 is a high intensityincandescent lamp such that several mw of power is introduced into atissue site, e.g. a finger, at each wavelength. The filter array 538utilizes multiple Fabry-Perot optical interference filters each having a10 nm bandwidth. The detector is a InGaAs photodiode having a 2 mm-3 mmdiameter, a useful response bandwidth in the range of 850 nm to 1700 nmand the highest possible intrinsic shunt resistance. The amplifier is atransimpedance amplifier such as Analog Devices 743, having a feedbackresistance in the range of 20 to 40 MΩ. The TDM signal output 412 (FIG.4) switches wavelengths at a 40 Hz rate.

FIG. 6 is a graph 600 having a logarithmic absorption axis 601 in unitsof cm⁻¹ versus a linear wavelength axis 602 in units of nm. Plotted onthe graph 600 is a water absorption curve 610 and glucose absorptioncurve 660. In a preferred embodiment, the pulse spectraphotometry systemis adapted to operate in a primary wavelength band 630 having a range ofabout 1620 nm to about 1730 nm. In a more preferred embodiment, thepulse spectraphotometry system is adapted to operate in a sub-band ofthe primary band 630 having a range of about 1620 nm to about 1670 nm.In a most preferred embodiment, the pulse spectraphotometry system isadapted to operate at a nominal wavelength of about 1650 nm±5 nm.

In a preferred embodiment, the pulse spectraphotometry system may alsobe adapted to operate in a secondary wavelength band 650 having a rangeof about 1000 nm to about 1380 nm. In a more preferred embodiment, thepulse spectraphotometry system may also adapted to operate at a nominalwavelength around about 1032 nm±5 nm and/or 1097 nm±5 nm, where waterand glucose are isobestic. The pulse spectraphotometry system may alsobe adapted to operate at a nominal wavelength around about 1375 nm±5 nmwhere water has about the same absorption as in the primary wavelengthband. Although the wavelength bands of about 1620 nm to about 1730 nmand of about 1000 nm to about 1380 nm are denoted above as primary andsecondary wavelength bands, respectively, the pulse spectraphotometrysystem may operate solely within the primary wavelength band, solelywithin the secondary wavelength band or concurrently within both bands.

As shown in FIG. 6, the preferred embodiment encompasses a criticalrange of wavelengths for a pulse spectraphotometry system, as describedherein. Water absorption rapidly increases an order of magnitude between1300 nm and 1400 nm and two orders of magnitude between 1300 nm and 1900nm. Water accounts for a significant percentage of blood, interstitialfluids and other tissue. Further, the intensity of optical radiationtransmitted through tissue decreases exponentially with absorption, asdescribed with respect to EQ. 1, above. Accordingly, for the same inputintensity, the detected output intensity, i.e. the DC output of thedetector 570 (FIG. 5), is roughly 200 times less at 1400 nm as comparedto 1300 nm. The result is that the signal drops below the electronicnoise present in the photodiode and preamp at wavelengths much above1300 nm. There is a small range of wavelengths in the primary band 630,which encompasses the preferred range of wavelengths, where it is verydifficult, but advantageous, to operate the pulse spectraphotometrysystem. Within this range, water absorption drops to a value roughlyequal to its value around 1380 nm, and it is possible to obtain aworking plethysmograph, but only by minimizing all noise sources,including the elimination of ambient light; the selection of low noiseelectronic components, such as described with respect to FIG. 5, above;and careful component layout and interconnection to avoid noise sourcessuch as crosstalk and ground noise, as is well-known in the art.

There are several advantages of the primary band 630 of wavelengths forthe spectraphotometric determination of certain blood constituents. Atleast five blood constituents of significance are in the near IR,including water, glucose, hemoglobin, urea and protein. In oneembodiment, the pulse spectraphotometry system operates over at leastfive wavelengths for resolution of these analytes. The absorptioncharacteristics of these analytes must be sufficiently different at theoperating wavelengths to insure a robust solution, as determined by thecondition number of the resulting matrix, as is well known in the art.Operating within the primary band 630 and the secondary band 650increases the variation in absorption characteristics. In particular,there is a crossover of water absorption and glucose absorption between1380 nm and 1620 nm, which allows glucose to be more easilydistinguished from water.

Another significant advantage of the primary band 630 is that glucoseabsorption is an order of magnitude larger within that band than for thesecondary band 650, i.e. at wavelengths below 1380 nm. Because intensityvaries exponentially with absorption, as described with respect to EQ.1, measurements derived from the primary band 630 are significantly moresensitive to variations in blood glucose than those derived from thesecondary band 650.

Yet another advantage to the primary band 630 is that, due to the higherabsorption of at least some blood constituents in the primary band,including water and glucose, the plethysmograph signal is larger inmagnitude in the primary band 630 than for the secondary band 650.Although the SNR of the plethysmograph signal is lower in the primaryband 630, the larger absolute magnitude provides a greater dynamic rangefor blood constituent measurements.

Although a primary band 630 and secondary band 650 are described abovewith respect to a sensor 500 (FIG. 5) configured to transmit lightthrough a tissue site 10 (FIG. 5), in another embodiment, the sensor 500(FIG. 5) may be configured to detect illumination reflected from atissue site 10 (FIG. 5). Because such a reflectance sensor suffers lesstissue absorption than a transmission sensor, the primary band 630 maybe somewhat broader, in the range of about 1575 nm to 1775 nm and atertiary band of wavelengths in the range of about 2000 nm to about 2500nm may be utilized.

A pulse and active pulse spectraphotometry system has been disclosed indetail in connection with various embodiments. These embodiments aredisclosed by way of examples only and are not to limit the scope of theclaims that follow. One of ordinary skill in the art will appreciatemany variations and modifications within the scope of this invention.

1. A pulse spectraphotometry system comprising: a light source adapted to illuminate a tissue site with optical radiation having a plurality of wavelengths selected from at least one of a primary band and a secondary band, said tissue site having a modulated blood volume; a detector configured to receive said optical radiation attenuated by said tissue site and to generate a detector output responsive to absorption of said optical radiation within said tissue site; a normalizer operating on said detector output to generate a plurality of normalized plethysmographs corresponding to said plurality of wavelengths; and a processor configured to calculate a ratio of fractional volumes of analytes in said blood volume based upon said normalized plethysmographs, wherein said secondary band is in a range of about 1000 nm to about 1380 nm.
 2. The pulse spectraphotometry system according to claim 1 wherein said primary band is in a range of about 1620 nm to about 1730 nm.
 3. The pulse spectraphotometry system according to claim 2 wherein said primary band is in a range of about 1620 nm to about 1670 nm.
 4. The pulse spectraphotometry system according to claim 3 wherein at least one of said wavelengths is selected in a range of about 1650 nm ±5 nm.
 5. The pulse spectraphotometry system according to claim 1 wherein at least one of said wavelengths is selected in a range of about 1032 nm±5 nm.
 6. The pulse spectraphotometry system according to claim 1 wherein at least one of said wavelengths is selected in a range of about 1097 nm±5 nm.
 7. The pulse spectraphotometry system according to claim 1 wherein at least one of said wavelengths is selected in a range of about 1375 nm±5 nm.
 8. A pulse spectraphotometry system comprising: a light source adapted to illuminate a tissue site with optical radiation having, a plurality of wavelengths the selected from at least one of a primary band and a secondary band, said tissue site having a modulated blood volume; a detector configured to receive said optical radiation attenuated by said tissue site and to generate detector output responsive to absorption of said optical radiation within said tissue site; a normalizer operating on said detector output to generate a plurality of normalized plethysmographs corresponding to said plurality of wavelengths; and a processor configured to calculate a ratio of fractional volumes of analytes in said blood volume based upon said normalized plethysmographs; wherein said detector is configured to receive said optical radiation after reflection from said tissue site and said wavelengths are further selected from a tertiary band of said wavelengths in a range of about 2000 nm to about 2500 nm.
 9. A pulse spectraphotometry method comprising the steps of: illuminating a tissue site having a pulsatile blood flow with a narrowband optical radiation; time division multiplexing said optical radiation over a plurality of wavelengths; selecting at least a portion of said wavelengths within a range of about 1620 nm to about 1730 nm; selecting a second portion of said wavelengths within a range of about 1000 nm to about 1380 nm; detecting an attenuated optical radiation from said tissue site as the result of said illuminating step; and calculating a ratio of analytes in said blood flow based upon said attenuated optical radiation.
 10. The pulse spectraphotometry method according to claim 9 wherein said selecting step comprises the substep of selecting at least one wavelength in a range of about 1620 nm to about 1670 nm.
 11. The pulse spectraphotometry method according to claim 9 wherein said selecting step comprises a substep of selecting at least one wavelength in a range of about 1650 nm±5 nm.
 12. The pulse spectraphotometry method according to claim 9 wherein said selecting a second portion step comprises a substep of selecting at least one wavelength in a range of about 1032 nm±5 nm.
 13. The pulse spectraphotometry method according to claim 9 wherein said selecting a second portion step comprises a substep of selecting at least one wavelength in a range of about 1097 nm±5 nm.
 14. The pulse spectraphotometry method according to claim 9 wherein said selecting a second portion step comprises a substep of selecting at least one wavelength in a range of about 1375 nm±5 nm.
 15. A pulse spectraphotometry system comprising: an optical radiation means for illuminating a tissue site; a filter means for determining a nominal and secondary wavelength of said optical radiation, said nominal wavelength selected from a range of about 1620 nm to about 1730 nm or from a range of about 2000 nm to about 2500 nm, said secondary wavelength selected from a range of about 1000 nm to about 1380 nm; a detector means for receiving said optical radiation after transmission through or reflection from said tissue site and generating a corresponding plethysmograph signal; and a processor means for calculating a ratio of analyte portions of pulsatile blood flow within said tissue site based upon said plethysmograph signal.
 16. The pulse spectraphotometry system according to claim 15 wherein said nominal wavelength is selected from a range of about 1620 nm to about 1670 nm.
 17. The pulse spectraphotometry system according to claim 16 wherein said nominal wavelength is selected from a range of about 1650 nm±5 nm.
 18. The pulse spectraphotometry system according to claim 15 wherein said secondary wavelength is selected from a range of about 1032 nm±5 nm.
 19. The pulse spectraphotometry system according to claim 15 wherein said secondary wavelength is selected from a range of about 1097 nm±5 nm.
 20. The pulse spectraphotometry system according to claim 15 wherein said secondary wavelength is selected from a range of about 1375 nm±5 nm.
 21. The pulse spectraphotometry system according to claim 15 wherein said nominal wavelength is selected from a range of about 2000 nm to about 2500 nm. 